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Biomedical subjects

S Hirose

Publications and source records attributed to S Hirose.

At least 199 records · Page 11Linked to original sources
PubMed1997

Transcriptional activation through interaction of MBF2 with TFIIA.

BACKGROUND: Transcriptional activation of the Drosopohila melanogaster fushi tarzu gene by FTZ-F1 or its silkworm counterpart BmFTZ-F1 requires two cofactors MBF1 and MBF2 which do not directly bind to DNA. MBF1 is a bridging molecule that connects FTZ-F1 (or BmFTZ- F1), MBF2 and TATA binding protein TBP. MBF2 is a positive cofactor that activates transcription. RESULTS: To elucidate the mechanism of transcriptional activation by MBF2, we isolated a cDNA coding for the factor. Northern blot analyses showed temporally restricted expression of MBF2 mRNA similar to that of BmFTZ-F1 mRNA. The cDNA sequence predicts a polypeptide of 10 kDa whereas natural MBF2 is a glycoprotein of 22 kDa. The deduced amino acid sequence of the factor showed no homology with proteins in the databases. Farwestern analyses and glutathione S-transferase interaction assays demonstrated that MBF2 makes a direct contact with the beta-subunit of TFIIA. In a HeLa cell nuclear extract, bacterially expressed recombinant MBF2 activated transcription from various promoters as natural MBF2 did. This activation requires the MBF2-TFIIA interaction. When recombinant MBF2 was added to the HeLa cell nuclear extract in the presence of MBF1 and FTZ622 bearing the DNA-binding region of FTZ-F1, it selectively activated transcription of the fushi tarazu gene. This selective activation also requires the MBF2-TFIIA interaction. CONCLUSION: MBF2 activates transcription through its interaction with TFIIA. Selective transcriptional activation occurs when MBF2 is recruited to a promoter carrying the FTZ-F1 binding site by FTZ-F1 and MBF1.

Amino Acid Sequence↗
PubMed1997

Temporal regulation of the mid-prepupal gene FTZ-F1: DHR3 early late gene product is one of the plural positive regulators.

BACKGROUND: Various ecdysteroid responsive genes play important roles in insect moulting and metamorphosis. Late FTZ-F1, a member of the nuclear receptor superfamily, is a unique transcription factor which is induced by a pulse exposure of 20-hydroxyecdysone. Elucidation of the regulation mechanism of this gene during prepupal period will help our understanding of metamorphosis at a molecular level. RESULTS: Using transgenic fly lines carrying various transcription regulatory regions of the FTZ-F1 gene fused to the LacZ gene, we investigated cis-regulatory elements in the late FTZ-F1 transcription unit. The region which governs the stage-specific expression during prepupal period was narrowed down to 1.2kb, from -0.7 to +0.5kb relative to the transcription start site. Electrophoresis mobility shift assays using staged extracts and various probes within the stage-specific region allowed us to identify binding sites for DHR3, an early late gene product, around 170 and 450bp downstream of the transcription initiation site. Mutations disrupting these binding sites reduced the reporter gene expression without affecting the stage specificity. CONCLUSIONS: Our deletion and mutation studies of the cis-regulatory element of the FTZ-F1 gene suggest that the DHR3 binding sites located in the 5' non-coding region are involved in the prepupal expression of the gene. These DHR3 binding sites confer high level expression while other elements are also involved in stage-specific expression.

Animals↗
PubMed1997

Apoptosis with FasL+ cell infiltration in the periphery and thymus of corrected autoimmune mice.

Fas (CD95) ligand (L) is a death factor that binds to its receptor, Fas, and induces apoptotic cell death, a crucial process in immunological tolerance. gld (generalized lymphoproliferative disorder) mice, which have a point mutation in the FasL gene, develop spontaneous systemic autoimmune syndromes characterized by hypergammaglobulinaemia and lymphoid hyperplasia owing to accumulation of abnormal B220+ CD3+ cells. Transplantation of wild-type (wt) bone marrow cells into old gld mice on the same strain background results in normalization of autoimmune syndromes. We characterized the cellular mechanisms (functionally and histologically) of the above phenomena in gld mice after bone marrow transplantation (BMT) to determine the role of apoptosis via Fas/FasL interactions in inducing and maintaining self-tolerance in vivo. Activated splenocytes from wt and BMT (wt to gld) mice showed significant cytotoxic activity against Fas transfectant cells while those from BMT (gld to gld) mice did not. Cells in the thymus, spleen and lymph nodes of gld mice uniformly upregulated Fas expression and were sensitive to Fas-mediated apoptosis compared with those in wt mice. Cells sensitive to Fas-mediated apoptosis in gld mice resided not only among abnormal B220+ CD3+ cells but also among conventional lymphocytes. More importantly, histological analysis revealed that cells in the spleen, lymph nodes and thymus frequently underwent apoptosis with infiltration of FasL+ cells in BMT (wt to gld) mice compared with BMT (gld to gld) mice. Our results indicated that apoptosis via Fas/FasL interactions can directly eliminate pathogenic cells responsible for autoimmunity in the periphery and possibly in the thymus in vivo.

Animals↗
PubMed1997

Detection of antibodies to a recombinant gag protein derived from human endogenous retrovirus clone 4-1 in autoimmune diseases.

To investigate whether human endogenous retroviruses (HERV) contribute to autoimmune diseases, we prepared a recombinant p30gag protein derived from clone 4-1 of the HERV family, using a baculovirus-vector system. This p30gag protein (CA41B) was approximately 30 kDa, as expected, and reacted with antibodies for p30gag purified from both murine and feline leukemia virus. This result suggested that the antigenic determinant for p30gag was well conserved in CA41B. Analysis of serum antibodies to p30gag in patients with autoimmune diseases was done by Western blotting. CA41B detected anti-p30gag antibodies in 48.3% of systemic lupus erythematosus (SLE) patients, 35.0% of Sjögren's syndrome (SS) patients, and 33.3% of mixed connective tissue disease (MCTD) patients, whereas no anti-p30gag antibodies were found in healthy subjects. This suggested that HERV p30gag or other retroviral p30gag proteins possessing the same antigenic determinant as CA41B may play a role in these diseases. Although detection of antibodies to HERV p30gag in autoimmune diseases is indirect evidence that HERV proteins are involved, this study showed that patients with autoimmune diseases have antibodies to HERV p30gag using a recombinant HERV protein rather than synthetic peptides based on HERV or retroviral proteins of other species.

Animals↗
PubMed1997

Is structural flexibility of antigen-binding loops involved in the affinity maturation of anti-DNA antibodies?

Effects of somatic mutations in Ig variable region genes on the affinity maturation of autoantibodies were investigated using single precursor B cell-derived anti-double-stranded DNA mAb generated from an autoimmune disease-prone (NZB x NZW)F1 mouse. Analyses of DNA sequences, homology modeling on a graphic computer and molecular dynamics simulation of antigen-binding sites showed that any single site of mutation and changes in the electrostatic or hydrogen-bonding potential of the residues and in the three-dimensional structure could not solely explain the difference in DNA-binding activities. However, a significant increase in the flexibility of antigen-binding Fv loops, particularly VL CDR1 and VH CDR3, was associated with affinity-maturated anti-DNA antibodies. Such high flexibility of the FV loops may provide the environment where the antibodies could effectively interact with antigen DNA, a model consistent with the 'induced-fit' hypothesis of antigen-antibody interactions.

Amino Acid Sequence↗
PubMed1997

Tissue distribution and localization of natriuretic peptide receptor subtypes in stroke-prone spontaneously hypertensive rats.

OBJECTIVE: To investigate tissue distribution and localization of the natriuretic peptide receptor (NPR) subtypes' messenger RNA (mRNA) and to compare their expression between stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto (WKY) rats. METHODS: Total RNA was extracted from organs of SHR-SP and WKY rats aged 13 weeks. The mRNA level was examined by RNase protection assay. The localization of the transcripts was determined by in-situ hybridization. RESULTS: In SHR-SP aged 13 weeks, NPR-A was expressed most abundantly in the adrenal gland, lung and aorta, in that order. NPR-B was expressed highly in the uterus and ovary, and also in the lung, adrenal, and brain. NPR-C was expressed predominantly in the atrium and mesentery, less so in the lung, vein, and kidney. In the adrenal gland, NPR-A was expressed mainly in zona glomerulosa cells. In the atrium, NPR-C was expressed throughout the wall. In the mesentery, NPR-C mRNA was detected mainly in adipocytes. In the kidney, NPR-C was found predominantly in podocytes. Whereas the levels of expression of NPR subtypes in most tissues examined did not differ between SHR-SP and WKY rats, the NPR-C mRNA level was significantly greater in the kidneys of SHR-SP than it was in those of WKY rats. CONCLUSIONS: These results indicated that each NPR subtype had a distinct tissue distribution pattern and that the expression of NPR-C in the kidneys of SHR-SP was greater than that in the kidneys of WKY rats.

Animals↗
PubMed1997

Role of curdlan sulfate in the binding of HIV-1 gp120 to CD4 molecules and the production of gp120-mediated TNF-alpha.

To clarify the mechanism by which curdlan sulfate (CRDS) inhibits human immunodeficiency virus (HIV)-1 infection, we examined its influence on the binding of gp120 to CD4 molecules on T cells and macrophages, as well as on the production of TNF-alpha by gp120-stimulated macrophages (which promotes HIV-1 replication). CRDS treatment of cells not only inhibited the binding of HIV-1 gp120 to CD4+ cells, but also inhibited TNF-alpha production induced by gp120. Inhibition of HIV-1 infection by CRDS may be related to these two actions.

Anti-HIV Agents↗
PubMed1997

Carnitine depletion during total parenteral nutrition despite oral L-carnitine supplementation.

Carnitine CAR) plays an important role in the beta-oxidation of fatty acids. Less attention. however, has been paid to CAR compared to other nutrients even in total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR level was measured in a 3-year-old boy receiving long-term TPN because of short bowel syndrome. Both the total and acyl CAR in the serum were evaluated under various nutritional conditions including oral supplementation of L-CAR. Low CAR concentrations were observed especially when lipid containing TPN regimens were in place. Oral L-CAR supplementation was not sufficient to restore the low CAR levels in the present index patient even when the dose was increased to 120 mg/kg in accordance with the result of the L-CAR absorption test that revealed poor intestinal absorption of this nutrient. Moreover, a markedly low CAR level was measured during the onset of sepsis in the patient, and the blood CAR was depleted when lipid metabolism was activated by lipid loading or sepsis. To date, the late effects of CAR depletion on child growth have not been well examined. It is recommended that the blood CAR level be maintained at normal levels before any prominent manifestations of the deficiency have developed. The intravenous administration of CAR appears to be necessary to supply a sufficient amount of CAR for patients with severe malabsorption.

Administration, Oral↗
PubMed1997

Human immunodeficiency virus type 2 envelope glycoprotein binds to CD8 as well as to CD4 molecules on human T cells.

We report here that human immunodeficiency virus type 2 (HIV-2) envelope glycoprotein (gp105), but not HIV-1 gp120, can bind to CD8 molecules as well as to CD4 molecules on human T cells. This phenomenon may lead to differences in the life cycles of HIV-1 and HIV-2, and it may be related to the differences in disease manifestations of HIV-1 and HIV-2 infection, including longer survival of HIV-2-infected patients.

CD4 Antigens↗
PubMed1997

Role of natriuretic peptide receptor type C in Dahl salt-sensitive hypertensive rats.

The natriuretic peptide system is suggested to be involved in the pathogenesis of salt-sensitive hypertension; a recent report indicated that disruption of the atrial natriuretic peptide precursor gene caused salt-sensitive hypertension. However, natriuretic peptide receptor (NPR)-A knockout mice did not show enhanced salt sensitivity of blood pressure. The aim of the present study was to investigate the role of NPR-C, the other receptor for atrial natriuretic peptide, in increased salt sensitivity of blood pressure. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were placed on a 0.3% or 8% NaCl diet for 4 weeks. Blood pressure was elevated by salt loading only in DS rats. RNase protection assay demonstrated that NPR-C transcript level in the kidney was reduced by chronic salt loading in both DR and DS rats, whereas expression of NPR-A and NPR-B was not altered. The reduction of NPR-C mRNA in response to salt loading was enhanced in DS compared with DR rats. In situ hybridization indicated that the salt-induced NPR-C change was attributed mainly to suppressed expression of NPR-C in the podocytes. NPR-C gene expression was regulated by salt loading in a tissue-specific manner; the marked decrease in NPR-C mRNA by salt loading was seen only in the kidney. These data suggest that the exaggerated salt-induced reduction of NPR-C in the kidney of DS rats may play an important role in the pathogenesis of salt hypertension in this animal, possibly related to impaired renal sodium excretion.

Animals↗
PubMed1997

Gene expression of endothelial type isoform of nitric oxide synthase in various tissues of stroke-prone spontaneously hypertensive rats.

Nitric oxide (NO) has been suggested to play important roles in the pathophysiology of various cardiovascular diseases. This study tested the hypothesis that an attenuated biological action of NO in hypertension is attributed to a change in the gene expression of NO synthase (NOS), a key enzyme involved in NO formation. The expression level of mRNA of endothelial type NOS (NOS-III) was determined in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and Wistar Kyoto rats (WKY/Izm) by ribonuclease protection assay using a partial clone as probe. NOS-III mRNA was expressed ubiquitously in various tissues of WKY/Izm and SHR-SP/Izm either at 5 wk or 13 wk of age. There was no significant difference in the tissue expression of NOS-III mRNA between the two strains at either age. The intensity and localization of the hybridization signal for NOS-III mRNA in the heart of SHR-SP/Izm did not differ from those in the heart of WKY/Izm. These results suggest that the attenuated biological action of NO implied in genetically hypertensive rats is not attributed to an abnormality at the level of NOS-III mRNA expression in the tissues, although lack of an increase in NOS-III gene expression, despite the hypertensive hemodynamic stress, may modify the blood pressure in hypertension.

Animals↗
PubMed1997

[A case of reactive arthritis fallen after shigellosis infection].

A 25-year-old woman was admitted for general arthralgia in July, 1989. Reactive arthritis with arthralgia after Shigellosis was diagnosed by sex, localization of arthralgia and positive for HLA-B 27. Within 3 weeks after starting diclifenac sodium 75 mg/day, the arthralgia remitted. It has been reported that patients who are positive for HLA-B 27 have a more severe acute or chronic sacroiliitis, and our case may support this report.

Adult↗
PubMed1997

Subsets of activated T cells in patients with systemic lupus erythematosus: the relation to cell cycle.

The correlation among the various markers of activated T cells (soluble interleukin 2 receptor (sIL-2R), HLA-DR+ and HLA-DP+ T cells, proliferating cell nuclear antigen (PCNA) positive lymphocytes) were examined in patients with systemic lupus erythematosus (SLE), and related to the cell cycle. The concentration of sIL-2R and the proportion of HLA-DR+ T cells, HLA-DP+ T cells or PCNA+ lymphocytes were increased significantly as compared to that in normal subjects. And, the concentrations of sIL-2R correlated with the proportions of PCNA+ lymphocytes, but not with the proportions of HLA-DR+ T cells, HLA-DP+ T cells. The correlation between sIL-2R and PCNA+ lymphocytes was attributed to both indicators being increased during the G1B or S phase in normal T cells upon stimulation by phytohemagglutinin (PHA). Upon cell cycle analysis it was learned that activated T cells could be found in the G1A and the S phases.

Adult↗
PubMed1997

Nodular regenerative hyperplasia of the liver in systemic lupus erythematosus. The relationship with anticardiolipin antibody and lupus anticoagulant.

Recent reports have indicated that nodular regenerative hyperplasia (NRH) associated with systemic lupus erythematosus (SLE) is related to anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). We describe a patient with SLE complicated by NRH, who did not show neither aCL nor LA activity. This case suggests that the pathogenesis of NRH in patients with autoimmune diseases is heterogeneous and not confined to aCL and LA.

Adult↗
PubMed1997

A hidden immunoglobulin G2 in patients with rheumatoid arthritis detected by nuclear magnetic resonance.

OBJECTIVE: The ratios of immunoglobulin (Ig) G1 and IgG2 in patients with rheumatoid arthritis (RA) were examined by nuclear magnetic resonance (NMR) and the results were compared to data obtained by ELISA. METHODS: The IgG of 11 patients with RA were prepared with a DE-52 column and the specific signals for IgG1 and IgG2 were measured by NMR. The ratios of IgG1 and IgG2 were determined by the intensity of this signal. The samples were also measured by ELISA. RESULTS: The ratios of IgG2 in patients with RA measured by NMR were increased significantly compared to controls. However, there were no significant differences in the data determined by ELISA. Thus, a discrepancy exists in the analysis of IgG2 ratios between NMR and ELISA methods. CONCLUSION: There was a discrepancy in the IgG2 ratios of patients with RA between NMR and ELISA methods, and we attribute this to a conformational difference in IgG2 in patients with RA.

Adult↗